Biomedical subjects

C Beglinger

Publications and source records attributed to C Beglinger.

243 records · Page 14Linked to original sources

PubMed1980

[Chemical structure and biological activity of cholecystokizin octapeptides with respect to the stomach and pancreas].

Dose response curves of the octapeptide of cholecystokinin (CCK-8) and 3 of its methoxinine analogues have been established in 4 conscious dogs with respect to gastric and pancreatic secretion. In the analogues the methionine was replaced by methoxinine in position 3 (B) and (D) or 6 (C). Of the 4 tested substances CCK-8 exhibited most activity with regard to pancreatic protein secretion, followed by B, C, and D. Analogue C had the strongest stimulating effect on gastric acid secretion, while its effect on pancreatic secretion was minor. Correlation of chemical structure with biological activity points to the importance of the methionine residue in position 6.

Animals↗

PubMedDate not supplied

[Modification of smoking behavior using long-distance methods].

906 persons willing to quit smoking were allocated at random to several groups. The results show that (1) an extract of avena sativa has no effect on quantity smoked; (2) distribution of the various parts of a smoking cessation program over several days was no more effective than distribution at once; (3) stopping at once was more effective than progressive reduction of cigarettes smoked.

Edible Grain↗

PubMedDate not supplied

Distinct hemodynamic and gastric effects of human CGRP I and II in man.

The human calcitonin gene-related peptides I and II (or alpha and beta) (CGRP I and II) are encoded by two different genes, but they have 34 of the 37 amino acid residues in common. Human CGRP I more potently stimulated blood flow through the skin and carotid artery (p less than 0.01), and the heart rate (p less than 0.05), and plasma renin activity and aldosterone secretion than human CGRP II (p less than 0.02). Inhibition of pentagastrin-stimulated gastric acid output, on the other hand, was only obtained with CGRP II. The separate effects of human CGRP I and II on the cardiovascular and gastric systems are presumably mediated by different receptors or receptor pathways recognized by the two closely related neuropeptides.

Adult↗

PubMedDate not supplied

Clinical outcome and quality of life after gastric and distal esophagus replacement with an ileocolon interposition.

Mainly because of the loss of reservoir function, loss of sphincter function, and exclusion of the duodenal route, patients who undergo gastrectomy suffer from many adverse effects postoperatively. The ileocecal interpositional graft is an attractive method to use as a gastric substitute after gastrectomy and distal esophagectomy. A pedunculated ileocecal graft is placed between the esophagus and the duodenum. The cecum acts as a reservoir while the ileocecal valve protects against enteroesophageal reflux. The duodenal passage is also preserved. Fourteen patients underwent this operation. The technique-related morbidity was low and the quality of life was good. During a mean follow-up of 6 months, no evidence of severe dumping syndrome or reflux esophagitis was observed. Further prospective randomized studies are warranted to compare this technique with the standard methods of gastric reconstruction.

Adult↗

PubMedDate not supplied

Effect of a liquid diet with and without soluble fiber supplementation on intestinal transit and cholecystokinin release in volunteers.

The effect of adding fiber to liquid formula diets on gastrointestinal transit is still controversial. Different fiber types (soluble vs insoluble) and different methodology of transit time measurements yielded variable results. Factors affecting transit include colonic fermentation, neural, and hormonal factors. We have therefore compared the effects of a standardized normal diet and two liquid formula diets with and without supplementation of a soluble fiber (21 g/L) on orocecal transit time measured by the hydrogen lactulose breath test, colonic transit time measured by radiopaque markers with an abdominal x-ray, bowel movements, stool consistency, and cholecystokinin release in 12 healthy male volunteers. The diets were consumed in a randomized order, each one for 7 days. The addition of soluble fiber did not affect orocecal transit time. Colonic transit time, however, was significantly prolonged (55 h) with fiber supplementation compared with the liquid diet (39 h) and the self-selected diet (30 h) (p < .01). Stool frequency and consistency was not significantly affected. During administration of both liquid diets, fasting cholecystokinin concentrations were significantly elevated compared with the concentrations found with a self-selected diet (p < .05). The fasting cholecystokinin concentration correlated significantly with the increase of segmental (right colon) colonic transit time (p = .02). The prolongation of colonic transit time in liquid diet-fed volunteers might be caused by the combined effect of increased colonic fermentation and high basal cholecystokinin concentrations.

Adult↗

PubMedDate not supplied

A microplate binding assay for the somatostatin type-2 receptor (SSTR2).

The clinical importance of somatostatin type-2 receptors (SSTR2) and the study of novel analogues of somatostatin such as OctreoScan or [Tyr3]-octreotide containing DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) as metal chelator led us to develop a methodology to monitor the expression of SSTR2 on tumours of pancreatic origin (e.g. rat AR4-2J cancer cells). Usual binding assay protocols using the commercial [125I][Tyr1]-somatostatin radioligand failed, even in the presence of a cocktail of protease inhibitors with a broad spectrum of activity, possibly due to the high susceptibility of this tracer to proteases expressed in pancreatic cells. We prepared our own radioligand [125I][Tyr2]-octreotide which was shown to be much more resistant to degradation after incubation with AR4-2J plasma membranes. As expected, the increased stability of [125I][Tyr3]-octreotide was associated with good binding to SSTR2. Addition of appropriate protease inhibitors further increased the specific binding of [125I][Tyr3]-octreotide to AR4-2J plasma membranes without affecting the stability of the tracer, suggesting that the protease inhibitors also protect the integrity of SSTR2. Optimal conditions (time, temperature, medium) were developed for a binding assay in 96-well plates using AR4-2J plasma membranes in order to make the assay suitable for high-throughput analysis. This protocol was the basis for studying the in vivo regulation of SSTR2 expression in AR4-2J cells implanted into scid mice after exposure to different compounds.

Animals↗

PubMedDate not supplied

A combinatorial peptoid library for the identification of novel MSH and GRP/bombesin receptor ligands.

A tripeptoid library was synthesized using 69 different primary amines in initially 69 individual reactions by the mix and split approach. The resulting library consisted of 328,509 (69(3)) single compounds, divided in 69 subpools each containing 4,761 entities. The 69 subpools were tested in two binding assays, one for alpha-MSH (alpha-melanotropin) and one for GRP (gastrin-releasing peptide)/bombesin. The sublibraries with the highest affinity to the MSH receptor (i.e. melanocortin type 1 or MC1 receptor) and, respectively, the GRP-preferring bombesin receptor were identified by an iterative process. Individual tripeptoids with good binding activity were resynthesized, analyzed and their dissociation constants and biological activity determined. The KD of the most potent MC1 receptor ligand was 1.58 mumol/l and that of the GRP-preferring bombesin receptor 3.40 mumol/l. Extension of this latter tripeptoid structure whose KD value increased to 280 nmol/l. A similar increase in activity was not observed with the most potent MSH tripeptoid ligand when extended by one residue, but a compound suitable for radioiodination and lacking the N-terminal amino group had a slightly higher binding activity than the tripeptoids (KD approximately 850 nmol/l). These results demonstrate that testing a peptoid library containing 328,509 single compounds led to the successful identification of new ligands for both the MC1 receptor as well as the GRP-preferring bombesin receptor.

Amino Acid Sequence↗

PubMedDate not supplied

Antiproliferative efficacy of the somatostatin analogue TT-232 in human melanoma cells and tumours.

BACKGROUND: TT-232, a somatostatin analogue, induces apoptosis in various tumours. The aim of our study was to characterise its effect on human melanoma cells and tumours. MATERIALS AND METHODS: Proliferation of seven melanoma cell lines was tested in vitro with the methylene blue test. D10 and 205 cells were also implanted into CB17-scid mice which received 30-150-750 micrograms/kg/day of TT-232 or saline. Animals with 205 cells received twice-daily subcutaneous injections whereas animals with D10 cells were treated with osmotic mini-pumps. In addition, TT-232 metabolites were generated with tissue homogenates and tested in vitro. RESULTS: TT-232 strongly inhibited proliferation of all cell lines in vitro and tumour growth in vivo. Two out of 8 animals (30-150 micrograms/kg) in the 205 model and one out of 8(150 micrograms/kg) in the D10 model became completely tumour-free at the 11th and 9th day of treatment, respectively. TT-232 was degraded only by liver homogenate whilst its metabolite had no antiproliferative effect in vitro. CONCLUSIONS: TT-232 is a promising drug candidate for melanoma.

Animals↗

PubMedDate not supplied

Tegaserod: a novel, selective 5-HT4 receptor partial agonist for irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a common functional bowel disorder of unknown aetiology. It is defined by the presence of gastrointestinal (GI) symptoms including abdominal pain/discomfort, bloating and bowel motor dysfunction. No available therapy is yet effective against all the symptoms of the disorder. Current treatments therefore target individual symptoms but may be accompanied by unpleasant side-effects. Tegaserod is a novel selective serotonin receptor type-4 (5-HT4) partial agonist with structural similarity to 5-HT Tegaserod stimulates small bowel and colonic motility and helps to normalise GI function. Clinical trials using a patient's assessment of efficacy demonstrate that tegaserod significantly improves key symptoms of IBS: abdominal pain/discomfort, bloating and constipation. Tegaserod is well tolerated with an excellent safety profile and represents a significant treatment advance in this difficult-to-treat disorder.

Clinical Trials, Phase III as Topic↗